Autoimmune diseases are thought to arise as a detrimental combination of genetic predisposition and environmental factors. Because of their potential for direct cellular damage and causing extensive inflammation, viruses are one of the major candidates for triggering autoimmunity. Although there is epidemiological evidence, direct proof for viruses as causative agents for autoimmune disease is hard to get since most viruses have been eliminated from the system by the time of diagnosis. However, evidence from various animal models suggests that viruses can indeed initiate or accelerate autoimmune diseases, such as type 1 diabetes or experimental allergic encephalomyelitis. In contrast, viruses have been also demonstrated to abrogate autoimmune disease in animal models. These observations might offer one explanation why increased frequencies of allergies and autoimmune diseases parallel with higher hygienic standards. This review reflects on the epidemiological evidence for the association of viruses with autoimmune diseases, the experimental evidence for viruses to abrogate an ongoing autoimmune destruction and evaluates the possibility for a therapeutic application.